8A z MONDAY, NOVEMBER 11, 2019 z USA TODAY NEWS

scription get labeled a potential cancer
risk? It’s a question the FDA, drug man-
ufacturers and consumers want an-
swered.
In September, the FDA found unac-
ceptable levels of the probable carcino-
gen NDMA, or nitrosodimethylamine, in
Zantac and generic medications. The
regulatory agency wants manufacturers
to test and recall the drugs if NDMA lev-
els exceed its standards. The FDA ex-
tended the voluntary recall to a similar
drug, nizatidine, sold under the brand
name Axid, if testing shows NDMA ex-
ceeding daily limits.
The FDA said consumers might want
to choose different medications. The
agency tested samples of over-the-
counter alternatives such as Pepcid, Ta-
gamet, Nexium, Prevacid and Prilosec
and found no NDMA.
The agency’s ranitidine investigation
seeks to uncover the root cause of NDMA
found in the commonly used medication.
Researchers at Memorial Sloan Kettering
Cancer Center in New York are assessing
whether people who used Zantac or its
generics face a greater cancer risk.
The warning first came after Valisure, a
Connecticut-based online pharmacy and
laboratory, discovered NDMA in several
forms of the drug and alerted the FDA.
The company said clues of the drug’s po-
tential risk can be traced to medical stud-
ies published since the early 1980s.
NDMA is the same carcinogen that
led to a widespread recall beginning in
July 2018 of the blood-pressure-lower-
ing drugs valsartan and losartan. The
blood pressure recall stemmed from a
new manufacturing process first used
by a drug ingredient factory in China.
Zantac’s risk appears to be the unsta-
ble nature of the drug itself, said Vali-
sure CEO David Light.
“This isn’t some new, bad manufac-
turing process overseas like what hap-
pened with valsartan and losartan,”
Light said. “It is our view that this prob-
lem with ranitidine has been there since
the 1980s.
“It’s a much more serious issue.”

‘Nobody found it’

Beyond the voluntary recalls, the
FDA is testing samples and published

testing standards for worldwide regula-

tors and drug manufacturers as it gath-

ers evidence on how the carcinogen is

formed.

Janet Woodcock, director of the

FDA’s Center for Drug Evaluation and

Research, told the House Committee on

Energy and Commerce on Oct. 30 that

the ranitidine carcinogen is a “different

problem” from other manufacturing

flaws such as drug ingredient contami-

nation in the blood pressure medication

recalls.

“This is a product that was approved

in 1984, and it’s used worldwide,” Wood-

cock told the committee. “And nobody

found it.”

The FDA asked pharmaceutical com-

panies to examine whether ranitidine’s

ingredients are exposed to nitrites dur-

ing manufacturing.

“Our chemists believe that it is

formed by the molecule ranitidine reac-

ting with something, either during the

manufacturing synthesis or during the

finished dosage form or during storage,”

Woodcock told the committee last

week.

The FDA studied how the drug reacts

with fluids in the stomach and intes-

tines. During such stimulated tests, the

FDA did not find evidence Zantac

formed carcinogens. The FDA said it

must test the drug in humans to evalu-

ate whether it forms NDMA.

Valisure tested Zantac in stomach-

like fluids with and without added ni-

trites, chemicals commonly found in

foods and the body. When those chem-

icals were added, Valisure found NDMA

levels for one tablet of Zantac reached

more than 3,100 times the FDA’s daily

threshold.

Light said testing the drug with add-

ed nitrites created “stomach relevant”

conditions.

“Ingesting nitrite-containing foods

like hot dogs can significantly increase

stomach levels of nitrite,” Light said.

“These foods are often eaten by indi-

viduals either before or after taking

antacid products.”

Studies in 1980s point to risk

In 2016, Stanford University re-

searchers tested urine samples of 10

people who took a 150-milligram tablet

of Zantac and found NDMA levels far

greater than the FDA’s daily limits.

William Mitch is a Stanford Univer-

sity professor of civil and environmen-

tal engineering who studies wastewa-

ter converted to drinking water. He

said his Zantac-urine study was a

“chance finding from a peripheral

field” after a study on potential NDMA

contamination in drinking water.

He said it should be followed by a

more robust study using the FDA’s

testing methods.

Lior Braunstein, a Memorial Sloan

Kettering oncologist and researcher, is

studying ranitidine and cancer risk.

He does not want to discuss the study

until the findings are published in a

peer-reviewed journal, according to

Caitlin Hool,a hospital spokeswoman.

Light said studies conducted in the

1980s raised concern about potential

safety risks. In a citizen petition to the

FDA, Valisure said Zantac’s originator,

Glaxo Research Group, conducted its

own study in 1987 “after numerous

studies raised concerns” about raniti-

dine.

The Glaxo study examined stomach

contents of people who took the drug.

It found people had no significant in-

crease in nitrosamines such as NDMA

within 24 hours of taking ranitidine.

Light said the study’s testing meth-

ods were less accurate and researchers

discarded stomach samples that con-

tained ranitidine. Without those sam-

ples, researchers would not find

NDMA or nitrosamines that form as a

result of taking the drug, Light said.

Light said the Stanford study and

his lab’s own analysis shows the po-

tential health risk for people who took

the drug.

“The negative effect of exposure to

this drug and its formation of NDMA is

something that has created a huge

public health problem,” he said, “and

we’re going to be dealing with it going

forward.”

Zantac

Continued from Page 1A

The FDA has found unacceptable levels

of the probable carcinogen NDMA, or

nitrosodimethylamine, in Zantac and

generic forms of the drug. It may have

been there for decades. GETTY

Trump to confront Turkey about

buying Russian defense system

President Donald Trump will con-

front Turkey’s leader about his deci-

sion to buy a Russian air defense sys-

tem when they meet this week at the

White House amid strained relations

between the two NATO allies.

Robert O’Brien, Trump’s national

security adviser, said Sunday the Unit-

ed States is still “very upset” by the

move to purchase the Russian S-

system. He told CBS’ “Face the Nation”

that if Turkey doesn’t get rid of the

Russian system, Turkey will likely face

U.S. sanctions.

Hispanic immigrant in line

to lead US Catholic bishops

Clergy sex abuse is once again on

the agenda as U.S. Catholic bishops

meet this week, but so is a potentially

historic milestone: Los Angeles Arch-

bishop Jose Gomez, an immigrant

from Mexico, is expected to win elec-

tion as the first Hispanic president of

the bishops’ national conference.

Gomez, 67, the conference’s vice

president, is considered a conserva-

tive, but he is an outspoken advocate

of an immigration policy that would

include a path to citizenship for many

immigrants in the U.S. illegally.

Rights group calls Iraqi

crackdown a ‘bloodbath’

Amnesty International said Sunday

that Iraq’s crackdown on anti-govern-

ment protests has descended into a

“bloodbath.”

At least 319 protesters have been

killed so far by security forces since

the unrest began last month, accord-

ing to the latest figures from the Iraqi

Human Rights Commission released

Sunday. Amnesty International said

Iraqi authorities should immediately

rein in security forces.

“The government of Iraq has a duty

to protect its people’s right to life, as

well as to gather and express their

views. This bloodbath must stop now,

and those responsible for it must be

brought to justice,” said Heba Morayef,

Amnesty International’s Middle East

and North Africa Director.

From staff and wire reports

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